The interaction of plasma coagulation factors with membranes is a central phenomenon in hemostasis and thrombosis. Present concepts favor the view that both the initiation and propagation of blood coagulation involve such interactions. Tissue factor is a component of many cell membranes which initiates that extrinsic system of coagulation. One of the aims of this program is to identify the anatomic location of these initiation sites, to elucidate the mechanism of the reactions and to establish the pertinent protein chemistry. An effort will be made to elucidate the structure of tissue factor and to investigate the physiological control of this system. Atheroma are intimately and probably causally related to thromboses. A principle aim of one of the projects is to develop and understanding of the molecular structure or early lesions, i.e., fatty streak deposits in human arteries. The possibility that thermotropic phase separations are involved in the mechanisms of accumulation and mobilization will be explored. The conversion of prothrombin to thrombin is catalyzed by activated factor X and markedly accelerated by factor V, phospholipids and calcium ions. This reaction is likely rate-limiting in coagulation and is thus probably an important step in physiological control. This reaction will be studied with regard to elucidating the stoichiometry of the reactants. Ultimately, the mechanism of action of the various accelerators will be studied. It is our hope that these studies will enable us to extend the current knowledge of the initiation, propagation and control of blood coagulation, hemostasis and thrombosis.